• Title/Summary/Keyword: differentiation-resistance

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Erratum to: Upstream signalling of mTORC1 and its hyperactivation in type 2 diabetes (T2D)

  • Ali, Muhammad;Bukhari, Shazia Anwer;Ali, Muhammad;Lee, Han-Woong
    • BMB Reports
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    • v.51 no.1
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    • pp.45-53
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    • 2018
  • Mammalian target of rapamycin complex 1 (mTORC1) plays a major role in cell growth, proliferation, polarity, differentiation, development, and controls transitioning between anabolic and catabolic states of the cell. It collects almost all extracellular and intracellular signals from growth factors, nutrients, and maintains cellular homeostasis, and is involved in several pathological conditions including, neurodegeneration, Type 2 diabetes (T2D), obesity, and cancer. In this review, we summarize current knowledge of upstream signaling of mTORC1 to explain etiology of T2D and hypertriglyceridemia, in which state, the role of telomere attrition is explained. We discuss if chronic inhibition of mTORC1 can reverse adverse effects resulting from hyperactivation. In conclusion, we suggest the regulatory roles of telomerase (TERT) and hexokinase II (HKII) on mTORC1 as possible remedies to treat hyperactivation. The former inhibits mTORC1 under nutrient-rich while the latter under starved condition. We provide an idea of TOS (TOR signaling) motifs that can be used for regulation of mTORC1.

Dual Drug-Loaded Liposomes for Synergistic Efficacy in MCF-7 Breast Cancer Cells and Cancer Stem Cells

  • Park, Hee-Bin;Kim, Yun-Ji;Lee, Seong-Min;Park, James S.;Kim, Keun-Sik
    • Biomedical Science Letters
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    • v.25 no.2
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    • pp.159-169
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    • 2019
  • Breast cancer stem cells (BCSCs) in breast cancer cells have self-renewal ability and differentiation potential. They are also resistant to drugs after chemotherapy. To overcome this resistance, we designed negatively charged 1,2-dimyristoyl-sn-glycero-3-phosphoglycerol (DMPG)-based liposomes for drug delivery. These liposomes have enhanced the therapeutic effects of a range of antitumor therapies by increasing the cellular uptake and improving drug delivery to targets sites. In this study, we investigated whether DMPG-POPC liposomes, including the neutral lipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholin (POPC), can specifically bind to MCF-7 breast cancer cells and increase cellular uptake compared with that by CHOL-POPC liposomes. We also estimated the cytotoxicity of DMPG-POPC liposomes encapsulated with both metformin (Met) and sodium salicylate (Sod) against breast cancer cells and BCSCs compared with that of the free drugs. Our results demonstrated that these dual drug-encapsulated liposomes significantly enhanced the cytotoxic and anti-colony formation abilities compared with individual drug-encapsulated liposomes or free drugs in BCSCs. Overall, our results suggest that DMPG-POPC liposomes containing two drugs (Met + Sod) show promise for synergistic anti-cancer therapy of breast cancer by increasing drug delivery efficiency into breast cancer cells and BCSCs.

Outbreak of Rice Blast Disease at Yeoju of Korea in 2020

  • Chung, Hyunjung;Jeong, Da Gyeong;Lee, Ji-Hyun;Kang, In Jeong;Shim, Hyeong-Kwon;An, Chi Jung;Kim, Joo Yeon;Yang, Jung-Wook
    • The Plant Pathology Journal
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    • v.38 no.1
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    • pp.46-51
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    • 2022
  • Rice blast is the most destructive disease threatening stable rice production in rice-growing areas. Cultivation of disease-resistant rice cultivars is the most effective way to control rice blast disease. However, the rice blast resistance is easy to breakdown within years by blast fungus that continually changes to adapt to new cultivars. Therefore, it is important to continuously monitor the incidence of rice blast disease and race differentiation of rice blast fungus in fields. In 2020, a severe rice blast disease occurred nationwide in Korea. We evaluated the incidence of rice blast disease in Yeoju and compared the weather conditions at the periods of rice blast disease in 2019 and 2020. We investigated the races and avirulence genes of rice blast isolates in Yeoju to identify race diversity and genetic characteristics of the isolates. This study will provide empirical support for rice blast control and the breeding of blast-resistant rice cultivars.

Breeding of inbred lines 'Wongyo 3115' and 'Wongyo 3116' in Strawberry (딸기 근교계통 '원교3115호'와 '원교 3116호' 육성)

  • Jeong, Ho Jeong;Lee, Sun Hee;Cho, Il whan;Rho, Il Rae
    • Horticultural Science & Technology
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    • v.33 no.3
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    • pp.443-447
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    • 2015
  • Fragaria ${\times}$ ananassa (Duch.) cultivars, 'Wongyo 3 115' a nd 'Wongyo 3 116', we re bre d as a n inte rme diate parent l ine using heterosis of $F_1$ hybrids in octoploid strawberry. These two new cultivars were developed as inbred lines ($S_9$ generation) propagated from both seed and runners/stolons. 'Wongyo 3115', an inbred line derived from the 'Benihoppe' cultivar, has a semi-upright plant shape showing a vigorless growth habit, weaker than the original 'Benihoppe' cultivar; it has early flower bud differentiation and produces 10 flowers per cluster when grown from healthy seed. 'Wongyo 3115' has low yields of conical type fruit with pink colored skin; average fruit weight is approximately 11 g. The important characteristic of 'Wongyo 3115' is its excellent fruit firmness, firmer than the original variety. 'Wongyo 3116', an inbred line derived from the 'Doyonoka' cultivar, has an upright plant shape, vigorless growth habit, weaker than that of the original 'Doyonoka' cultivar; it has early flower bud differentiation and produces 8 flowers per cluster when grown from healthy seed. 'Wongyo 3 116' has oblate type fruits with red skin and an ave rage weight of approximately 12 g. The important characteristics of 'Wongyo 3116' are excellent fruit shape and higher yield than other inbred lines, although it produces small fruits compared to the original cultivar. Both cultivars have excellent taste, high sugar/acid ratio, and good texture. In regards to disease and pest resistance, 'Wongyo 3115' and 'Wongyo 3116' have a tendency to be sensitive to powdery mildew, anthracnose and the two-spotted spider mite.

Insulin Sensitizing and Insulin-like Effects of Water Extracts from Kalopanax pictus NAKAI in 3T3-L1 Adipocyte (엄나무 추출물이 3T3-L1 지방세포에서 인슐린 민감성과 인슐린 유사성 작용에 미치는 영향)

  • Kim, Ho-Kyoung;Park, Sun-Min;Ko, Byoung-Seob
    • Applied Biological Chemistry
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    • v.45 no.1
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    • pp.42-46
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    • 2002
  • Effects of the water extract from Kalopanax pictus NAKAI on insulin-like action and glucose uptake in 3T3-L1 cells were investigated. The bark of K. pictus NAKAI was treated with hot water and the extract was freeze-dried. Total extract of K. pictus NAKAI was fractionated into 6 fractions with increasing gradients from 0 to 100% MeOH on Amberlite XDA-4. Treatment of 3T3-L1 fibroblasts with 1 ${\mu}g/ml$ and 10 ${\mu}g/ml$ of K. pictus NAKAI total extracts significantly increased the differentiation of the cells. When co-treated with inducers such a dexamethasone, 1-methyl-3-isobutylxanthine and insulin, the differentiation was increased at 1 ${\mu}g/ml$ of total extract, but not at 10 ${\mu}g/ml$. In 3T3-L1 adipocytes, glucose uptake was increased by 3.3 times with addition of 0.3 and 3 ${\mu}g/ml$ of Fr. 1 (0-10% MeOH) and Fr. 3 (30% MeOH) at 3 ng/ml insulin. In conclusion, K. pictus NAKAI contains such compounds that play a role of insulin-like action and insulin sensitizer.

Genetic Variations Analysis and Characterization of the Fifth Intron of Porcine NRAMP1 Gene

  • Yan, X.M.;Ren, J.;Ai, H.S.;Ding, N.S.;Gao, J.;Guo, Y.M.;Chen, C.Y.;Ma, J.W.;Shu, Q.L.;Huang, L.S.
    • Asian-Australasian Journal of Animal Sciences
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    • v.17 no.9
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    • pp.1183-1187
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    • 2004
  • The natural resistance-associated macrophage protein 1 (NRAMP1) gene was identified as a candidate gene controlling the resistance and susceptibility to a number of intracellular parasites in pigs. The genetic variations in a 1.6 kb region spanning exon 1 and exon 3 of the porcine NRAMP1 gene were investigated by PCR-HinfI-RFLP in samples of 1347 individuals from 21 Chinese indigenous pig populations and 3 western pig breeds. Three alleles (A, B, C) and four genotypes (AA, BB, AB, BC) were detected. Significant differences in genotype and allele frequencies were observed between Chinese indigenous pig populations and exotic pig breeds, while in general the differences in genotype and allele frequencies among Chinese indigenous pig populations were not significant. The allele C was detected only in Duroc, Leping Spotted and Dongxiang Spotted pig, and the two Chinese pig populations showed similar genotype and allele frequencies. Four Chinese Tibetan pig populations displayed genetic differentiation at the NRAMP1 gene locus. In addition, intron 5 of the NRAMP1 gene was isolated and characterized by directly sequencing the PCR products encompassing intron 5. The alignment of intron 5 of the porcine, human, equine and ovine NRAMP1 gene showed a similarity of 45.38% between pig and human, 52.55% between pig and horse, 63.47% between pig and sheep, respectively.

Physiological Characteristics and Anti-Obesity Effect of Enterococcus faecalis MD366 isolated from Raw Milk (원유에서 분리한 Enterococcus faecalis MD366의 생리적 특성 및 비만 억제 효과)

  • Park, Sun-Young;Cho, Seong-A;Han, Noo-Ri;Lim, Sang-Dong
    • Journal of Dairy Science and Biotechnology
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    • v.32 no.2
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    • pp.147-156
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    • 2014
  • The aim of this study was to investigate the physiological characteristics and anti-obesity effects of E. faecalis MD366 isolated from raw milk. E. faecalis MD366 inhibited lipase activity ($65.0{\pm}0.9%$) and differentiation of 3T3-L1 adipocytes ($27.4{\pm}1.4%$) at a concentration of $100{\mu}g/mL$ ($10^8CFU/g$ E. faecalis MD366). The optimum growth temperature of E. faecalis MD366 was $37^{\circ}C$. Among 16 tested antibiotics, E. faecalis MD366 demonstrated the highest sensitivity to novobiocin and the highest resistance to neomycin, kanamycin, and vancomycin. The strain also showed high acid phosphatase activity. Moreover, E. faecalis was relatively tolerant to bile juice and acid, and displayed high resistance to Escherichia coli, Salmonella Typhimurium, and Staphylococcus aureus (80.4%, 60.2%, and 65.4%, respectively). These results demonstrate that E. faecalis MD366 can be potentially used as a probiotic with anti-obesity effects.

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The Significance of Cancer Stem Cells in Canine Mammary Gland Tumors (개 유선종양 내 종양줄기세포의 중요성)

  • Park, Seo-Young;Baek, Yeong-Bin;Park, Sang-Ik;Lee, Chang-Min;Kim, Sung-Hak
    • Journal of Life Science
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    • v.31 no.2
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    • pp.248-255
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    • 2021
  • Mammary gland tumors are one of the most common cancers in female dogs, and there are various types of cells depending on the tumor type. Complex carcinoma consists of a combination of luminal epithelial and myoepithelial cells with intra-tumoral heterogeneity. However, the origins of these tumor cells and their effects on the malignancies of tumors have not been identified. Recently, it has been reported that cancer stem cells, identified in several types of human tumors, are involved in tumor heterogeneity and may also contribute to malignancies such as tumor recurrence and metastasis. Interestingly, cancer stem cells share several abilities of self-renewal and cell differentiation into multiple types of cancer cells, but they have abnormal genetic mutation and signal transduction pathways to regulate the maintenance of stem cell characters. Moreover, it is known that these cell populations contribute to cell metastasis as well as cell resistance against chemo- and radio-therapeutics that promote tumor recurrence. The existence of cancer stem cells might explain the intra-tumoral heterogeneity and cancer aggressiveness during tumorigenesis in canine mammary gland tumors. This review summarizes the characteristics and types of canine mammary gland tumors, the definition of tumor stem cells, methods of isolation, and clinical significance.

Serum Level of MMP-3 in Patients with Oral Squamous Cell Carcinoma - Lack of Association with Clinico-pathological Features

  • Tadbir, Azadeh Andisheh;Purshahidi, Sara;Ebrahimi, Hooman;Khademi, Bijan;Malekzadeh, Mahzad;Mardani, Maryam;Taghva, Masumeh;Sardari, Yasaman
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.9
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    • pp.4545-4548
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    • 2012
  • Background: MMP-3 is a proteolytic enzyme of the matrix metalloproteinase family. Protein degradation which is their fundamental action regulates different activities of tumor cell such as their growth, differentiation, apoptosis, migration, invasion, angiogenesis as well as their resistance to the immune system. Aim: The aim of this study was to determine MMP-3 serum levels in patients with OSCC and investigate if they correlate with clinicopathological features. Method and materials: Using an ELISA kit, we assessed and compared the circulating levels of MMP-3 in blood serum of 45 oral squamous cell carcinoma patients with 45 healthy control samples. Results: The serum MMP-3 level in OSCC patients was significantly higher ($9.45{\pm}4.6$ ng/ml) than healthy controls ($5.9{\pm}3.6$ ng/ml, p<0.001), especially in females and in older patients. However, there was no apparent correlation in serum MMP-3 concentration with the clinico-pathological features such as tumor location, stage, tumor size, nodal status, distant metastasis, histological grade and smoking. Discussion: This result suggests that the measurement of serum MMP-3 concentration might be helpful to diagnose OSCC but not to predict prognosis.

Multi-resistance strategy for viral diseases and in vitro short hairpin RNA verification method in pigs

  • Oh, Jong-nam;Choi, Kwang-hwan;Lee, Chang-kyu
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.4
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    • pp.489-498
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    • 2018
  • Objective: Foot and mouth disease (FMD) and porcine reproductive and respiratory syndrome (PRRS) are major diseases that interrupt porcine production. Because they are viral diseases, vaccinations are of only limited effectiveness in preventing outbreaks. To establish an alternative multi-resistant strategy against FMD virus (FMDV) and PRRS virus (PRRSV), the present study introduced two genetic modification techniques to porcine cells. Methods: First, cluster of differentiation 163 (CD163), the PRRSV viral receptor, was edited with the clustered regularly interspaced short palindromic repeats-CRISPR-associated protein 9 technique. The CD163 gene sequences of edited cells and control cells differed. Second, short hairpin RNA (shRNAs) were integrated into the cells. The shRNAs, targeting the 3D gene of FMDV and the open reading frame 7 (ORF7) gene of PRRSV, were transferred into fibroblasts. We also developed an in vitro shRNA verification method with a target gene expression vector. Results: shRNA activity was confirmed in vitro with vectors that expressed the 3D and ORF7 genes in the cells. Cells containing shRNAs showed lower transcript levels than cells with only the expression vectors. The shRNAs were integrated into CD163-edited cells to combine the two techniques, and the viral genes were suppressed in these cells. Conclusion: We established a multi-resistant strategy against viral diseases and an in vitro shRNA verification method.